Ropeginterferon alfa-2b in hydroxyurea-intolerant or hydroxyurea-refractory essential thrombocythaemia (SURPASS ET): a multicentre, open-label, randomised, active-controlled, phase 3 study.

A standard second-line agent has been anagrelide.

标准的二线药物一直是阿那格雷。

Ropeginterferon alfa-2b, a new-generation interferon-based therapy, is approved for polycythaemia vera.

Ropeginterferon alfa-2b，一种新一代干扰素为基础的疗法，已被批准用于真性红细胞增多症。

We aimed to assess efficacy and safety of ropeginterferon alfa-2b compared with anagrelide in patients with essential thrombocythaemia with leukocytosis who are intolerant or resistant to hydroxyurea.

我们的目标是评估Ropeginterferon alfa-2b与Anagrelide在对羟基脲不耐受或耐药的伴有白细胞增多的原发性血小板增多症患者中的疗效和安全性。

Methods

The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 109 cells/L.

SURPASS ET是一项开放标签、随机、活性对照的3期临床试验，在中国、日本、台湾、香港、韩国、美国、新加坡和加拿大共55个临床中心进行，招募了18岁及以上的高危患者（年龄>60岁且携带JAK2 Val617Phe突变或有疾病相关血栓或出血史）、对羟基脲不耐受或耐药的原发性血小板增多症患者，且白细胞计数超过10 × 10^9个细胞/L。

Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country.

患者按1:1的比例随机分配至ropeginterferon alfa-2b或anagrelide治疗组，根据血小板计数、症状评分和国家进行分层。

Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward.

罗派干扰素alfa-2b每两周皮下给药一次，初始剂量为250微克，随后在第2周调整至350微克，并从第4周起调整至500微克。

Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information.

阿那格雷根据美国食品药品监督管理局批准的处方信息口服给药。

The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria.

主要终点是根据修改后的欧洲白血病网络（ELN）标准，在第9个月和第12个月的反应率。

The main planned analysis for the study was done in the intention-to-treatpopulation.

该研究的主要计划分析是在意向治疗人群中进行的。

The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing.

该试验已在ClinicalTrials.gov注册，编号为NCT04285086，并已完成。目前正在进行一项扩展研究，以收集长期数据。

Results

Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide).

在2020年8月25日至2024年11月12日期间，共有245名患者接受了筛查，其中174名被随机分配（91名接受ropeginterferon alfa-2b治疗，83名接受anagrelide治疗）。

The median follow-up was 12·5 months (IQR 11·5-12·9).

中位随访时间为12.5个月（四分位数间距11.5-12.9）。

At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White.

在基线时，91名接受ropeginterferon alfa-2b治疗的参与者中有47名（52%）为女性，而在83名接受anagrelide治疗的参与者中有44名（53%）为女性。174名参与者中有167名（96%）为亚洲人，7名（4%）为白人。

The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group.

该试验达到了其主要终点，91名接受ropeginterferon alfa-2b治疗的参与者中有39人（43%）在第9个月和第12个月时显示出持久的改良ELN标准反应，而接受anagrelide治疗的83名参与者中仅有5人（6%）显示出类似反应。

This difference (36·5%, 95% CI 25·4-47·7) was significant (p=0·0001).

这一差异（36.5%，95% 置信区间25.4-47.7）是显著的（p=0.0001）。

Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group.

在阿那格雷组的80名患者中，有27名（34%）出现了3级或更严重的治疗后不良事件，而在罗格干扰素α-2b组的91名患者中，有21名（23%）出现了3级或更严重的不良事件。

In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group.

在罗格干扰素α-2b组中，最常见的是3级或更严重的不良事件，包括感染和寄生虫病，共有8名（9%）患者出现，而在阿那格雷组的80名患者中，有5名（6%）出现此类不良事件。

In the anagrelide group, the most frequent grade 3 or worse adverse events were nervous system disorders, occurring in six (8%) of 80 patients, compared with one (1%) of 91 patients with ropeginterferon alfa-2b.

在阿那格列德组中，最常见的3级或更严重的不良事件是神经系统疾病，发生在80名患者中的6名（8%），而罗格干扰素α-2b组的91名患者中只有1名（1%）。

Serious adverse events occurred in 24 (30%) of 80 participants in the anagrelide group and 13 (14%) of 91 participants in the ropeginterferon alfa-2b group).

在阿那格列德组的80名参与者中，有24名（30%）发生了严重不良事件，而在罗格干扰素α-2b组的91名参与者中，有13名（14%）发生了严重不良事件。

The most common serious adverse eventwas cerebral infarction, which occurred in four (5%) of 80 patients in the anagrelide group but was not observed in the ropeginterferon alfa-2b group.

最常见的严重不良事件是脑梗死，发生在阿那格雷组的80名患者中的四名（5%），但在罗格替尼干扰素alfa-2b组中未观察到。

There were no treatment-related deaths in either study group.

在两个研究组中均未出现与治疗相关的死亡。

interpretation

Our findings suggest that ropeginterferon alfa-2b could be considered as a second-line treatment option for patients with essential thrombocythaemia and leukocytosis.

我们的发现表明，对于伴有血小板增多症和白细胞增多的患者，Ropeginterferon alfa-2b可以被视为一种二线治疗选择。

funding

PharmaEssentia.

PharmaEssentia公司。